68 results about "Benzodiazepine Compounds" patented technology

The present invention relates to novel pyrrolo[2,1-c][1,4]benzodiazepines compounds of general formula V as shown below, which are useful as potential antitumour agents and a process of preparing these compounds; particularly the present invention provides a process for the preparation of 7-methoxy-8-{n-[7-methoxy-(11aS)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]ben-zodiazepine-5-one-8-yloxy]alkyloxy}-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one, with varying aliphatic chain length and its 2-hydroxy derivatives.

Benzodiazepinc compounds, and methods for using those compounds are provided. Some of the benzodiazepine compounds include 1,4-benzodiazepine-2-one and 1,4-benzodiazepine-2,5-dione compounds of structures (I) or (II): wherein R1, R2, R3 and R4 are as defined. The invention also includes enantiomers, pharmaceutically acceptable salts, prodrugs or derivatives of the benzodiazepine compounds. Any one or more of these benzodiazepine compounds can be used to treat a variety of dysregulatory disorders related to cellular death. Such disorders include autoimmune disorders, inflammatory conditions, hyperproliferative conditions, viral infections, and atherosclerosis. In addition, the above compounds can be used to prepare medicaments to treat the above-described dysregulatory disorders. The benzodiazepines can also be used in drugs screening assays and other diagnostic methods.

The present invention relates to novel chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides benzodiazepine derivatives and related compounds and methods of using benzodiazepine derivatives and related compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, and the like.

The present invention relates to novel chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides benzodiazepine compounds, and structurally and functionally related compounds, and methods of using such compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, vascular abnormalities, and the like.

Benzodiazepine compounds, and methods for using those compounds are provided. Some of the benzodiazepine compounds include 1,4-benzodiazepine-2-one and 1,4-benzodiazepine-2,5-dione compounds of the following structures: wherein R1, R2, R3 and R4 are as defined. The invention also includes enantiomers, pharmaceutically acceptable salts, prodrugs or derivatives of the benzodiazepine compounds. Any one or more of these benzodiazepine compounds can be used to treat a variety of dysregulatory disorders related to cellular death. Such disorders include autoimmune disorders, inflammatory conditions, hyperproliferative conditions, viral infections, and atherosclerosis. In addition, the above compounds can be used to prepare medicaments to treat the above-described dysregulatory disorders. The benzodiazepines can also be used in drug screening assays and other diagnostic methods.

The present invention relates to novel chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides benzodiazepine derivatives and related compounds and methods of using benzodiazepine derivatives and related compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, and the like.

Compounds and a method of synthesis of compounds of formula (Ia) or (Ib): and salts, solvates, and chemically protected forms thereof, wherein the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; R2 and R3 are independently selected from —H, ═O, ═CH2, —CN, —R, OR, halo, ═CH—R, O—SO2—R, CO2R and COR; R10 is a carbamate-based nitrogen protecting group; and R11 is an oxygen protecting group.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VI). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

The invention discloses a method for quickly detecting the doping of a benzodiazepine compound in a food, a medicine or a health-care product. The method comprises the following steps: firstly, preprocessing a sample to be measured, extracting the benzodiazepine compound which is added in an enriched transgression way and then combining with a colloidal gold immunological chromatographic method, thereby realizing the quick detection of the benzodiazepine compound added into the food, the medicine or the health-care product.The invention features wide coverage range of measured targets, simple operation, high detection speed and easy observation of a detection result, can realize the quick screening of a large number of samples, picks out the samples added with the benzodiazepine compound in a transgression way from a large number of samples, lowers the cost greatly and reduces the workload.The preprocessing method can effectively enrich the concentration of a substance to be measured, so the detection result is more sensitive and accurate.The invention is suitable for various common medicament forms in the food, the medicine or the health-care product, can fill up a system screening method which is absent in the industry, executes the supervision and control over the food and medicine market effectively and guarantees the safety of the diet and medicine of people.

The invention relates to a method for preparing a thieno-benzodiazepine compound. The following main steps are that the thieno-benzodiazepine compound is prepared by a compound as shown in the formula (2) and a compound as shown in the formula (3) by carrying out condensation reaction, reduction reaction and cyclization reaction in sequence; the method is characterized in that i) the reducer adopted in the reduction reaction can be Fe, FeSO4, Zn, Na2S, Na2S2 or NaHS; ii) before the reduction reaction is carried out, the unreacted compound as shown in the formula (2) needs to be removed. The preparation method has the advantages of simple and easy operation (facilitating commercial preparation), moderate reaction conditions, low preparation cost of the products, high purity and yield of the products, and so on. The preparation method lays a foundation for the enhancement of the commercial preparation of the ultimate products which take the thieno-benzodiazepine compound prepared by the invention as an intermediate.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VI). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

The present invention relates to substituted heterocyclic compounds and substituted tetrahydroisoquinoline compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzodiazepine compounds and substituted tetrahydroisoquinoline compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds or pharmaceutical compositions to subjects in need thereof.

The invention relates to a method for preparing benzodiazepine compounds, and discloses a method for preparing 8-R2-6-(2-R1-phenyl)-1-methyl-3a,4-dihydro-3H-imidazo[1,5-a][1,4] benzodiazepine (midbody II) and 8-R2-6-(2-R1-phenyl)-1-methyl-4H-imidazo[1,5-a][1,4] benzodiazepine (product III), wherein R is hydrogen, fluorine, chlorine, bromine or iodine; R2 is fluorine, chlorine, bromine or iodine. The midbody II is prepared from 7-R2-5-(2-R1-phenyl)-2-aminomethyl-2,3-dihydro-1H-[1,4] benzodiazepine and triethyl orthoacetate as raw materials through ultrasonic reaction; the product III is prepared by performing enzyme dehydrogenation on the midbody II. By adopting the technical scheme of the invention, the dehydrogenation reaction selectivity is improved, and the reaction yield is improved.

The invention relates to pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) of formula (I) and in particular to PBD dimers linked through the C1 position, and PBD monomers linked through the C1 position to aromatic groups, and pharmaceutically acceptable salts thereof, which are useful as medicaments, in particular as anti-proliferative agents. (I) and salts or solvates thereof, wherein: the dotted lines indicates the optional presence of a double bond between C1 and C2 or C2 and C3; R2-R7 are independently selected substituent groups; and either: (i) R8 and R9 together form a double bond; (ii) R8 is H and R9 is OH; or (iii) R8 is H and R9 is ORA and RA is C1-6 alkyl; where R1 has the formula: —X-L-X′-D-X-L-X′— is a linker group and D has the formula (II) or (III): or where the compound is a dimer with each monomer being the same or different and being of formula (I) where the R1 of the first monomer and R′1 or R′6 of the second monomer, or R6 of the first monomer and R′1 of the second monomer, form together a bridge having the formula —X-L-X′— linking the monomers.

The present invention relates to novel chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides benzodiazepine compounds, and structurally and functionally related compounds, and methods of using such compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, vascular abnormalities, and the like.

The invention provides a benzodiazepine compound as well as a preparation method and a pharmaceutical effect thereof, and belongs to the field of chemical medicines. The benzodiazepine compound is a compound shown as a formula I, or a salt thereof, or a stereoisomer thereof, or a solvate thereof, or a eutectic thereof, or a composition thereof. The compound is good in intravenous sedative anesthesia effect, the anesthesia effect of the compound is equivalent to or even superior to that of remimazolam, and specifically, the effective dosage is remarkably reduced, and the duration time and the recovery time are remarkably shortened. Meanwhile, in rat and mouse caudal vein anesthesia models, compared with remimazolam, the compound has remarkably improved waking quality. The compound providedby the invention has the advantages of fast onset, short duration, fast awakening and good tolerance during anesthesia, can be used for anesthesia induction, anesthesia maintenance and daytime operation anesthesia, and has a good application prospect.

The invention provides a family of 1,4-benzodiazepinone compounds and methods for their use as therapeutic agents in treating cancer. Pharmaceutical compositions and methods of making the 1,4-benzodiazepinone compounds are provided.

The invention discloses 1,3-benzodiazepine compounds with anticancer activity and a synthesis method thereof, and belongs to the technical field of drug development. The structural general formula ofthe 1,3-benzodiazepine compounds is shown in the specification; and the synthesis method comprises the following steps: mixing N-aryl amidine 1, propargyl alcohol ester compounds 2, a rhodium or ruthenium catalyst, an additive and an organic solvent, and performing heating and reacting to obtain the 1, 3-benzodiazepine compounds 3. The synthesis method disclosed by the invention has the advantagesof simple and easily available raw materials, simplicity and convenience in operation, mild conditions, wide substrate application range and the like, and the compounds have remarkable inhibitory activity on cancer cells such as HeLa or Ramos and are potential candidate drug molecular structures.

The present invention relates to benzodiazepine derivative compounds of formula (I), or pharmaceutically acceptable salts thereof. The present benzodiazepine compounds are useful Clostridium difficile inhibitors in the treatment of Clostridium difficile infection in humans. The present invention provides a pharmaceutical composition containing benzodiazepine compounds of formula (I) and a method of making as well as a method of using the same in treating patients infected with Clostridium difficile infection by administering the same. The compounds of the present invention may be used in combination with additional antibiotics or anti-toxin antibody drugs.

The present invention relates to novel pyrrolo[2,1-c][1,4]benzodiazepines compounds of general formula V as shown below, which are useful as potential antitumour agents and a process of preparing these compounds; particularly the present invention provides a process for the preparation of 7-methoxy-8-{n-[7-methoxy-(11aS)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]ben-zodiazepine-5-one-8-yloxy]alkyloxy}-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one, with varying aliphatic chain length and its 2-hydroxy derivatives.

The invention discloses a method for catalytically preparing a benzodiazepine compound by using titanocene dichloride. According to the method, a 3-butyne-2-ketone compound and an o-phenylenediamine compound are taken as raw materials, ethanol or methanol is taken as a solvent and an accelerant, titanocene dichloride is taken as a catalyst, and isophthalic acid and 2-hydroxy nicotinic acid or salicylic acid is taken as a ligand to high efficiently prepare the 2,4-diphenyl-3-H-1,5-benzodiazepine derivative in a high-yield mode. The usage amount of the catalyst used in the method is low, and the catalyst is low in price, is free of toxicity and is stable in air; the reaction is mild in conditions, short in time and simple in operation; and after the reaction is finished, only simple column chromatography separation is needed to be carried out on the product to obtain the 2,4-diphenyl-3-H-1,5-benzodiazepine derivative. A novel low-cost green and efficient way is developed for preparation of the 2,4-diphenyl-3-H-1,5-benzodiazepine derivative, and the method has a wide application prospect.

The invention is directed to novel [1,4]benzodiazepine compounds useful as vasopressin receptor antagonists for treating conditions involving increased vascular resistance and cardiac insufficiency. Pharmaceutical compositions comprising [1,4]benzodiazepine compounds of the present invention and methods of treating conditions such as hypertension, congestive heart failure, cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, renal vasospasm, renal failure, cerebral edema and ischemia, stroke, thrombosis, or water retention are also disclosed.

The invention relates to a preparation method of a benzodiazepine compound, which comprises the following steps: reacting amino functionalized ionic liquid, phenylpropyl aldehyde, Boc-anthranilic acid and cyclohexyl isonitrile to obtain an ionic-liquid-loaded Ugi product; reacting the ionic-liquid-loaded Ugi product under the catalytic action of hydrogen chloride gas to obtain a benzodiazepine compound of which the side chain is modified by Ugi reaction; and carrying out rotary evaporation on the reaction liquid, and washing out residues with anhydrous aether to obtain the required benzodiazepine compound. Compared with the existing preparation method, the preparation method provided by the invention shortens the reaction procedures and enhances the reaction efficiency; and the synthesis method is simple and efficient, and has wide application prospects.

The invention provides 1,4-benzodiazepinone compounds, pharmaceutical compositions, and methods of treating autoimmune disorders, chronic inflammatory disorders, and hyperproliferative disorders. For example, the 1,4-benzodiazepinone compounds and pharmaceutical compositions are contemplated to be useful for treating rheumatoid arthritis, graft-versus-host disease, inflammatory bowel disease, and the like.

The invention discloses application of a 5-hydrogen-1,4-benzodiazepine compound in treatment of the liver cancer. The 5-hydrogen-1,4-benzodiazepine compound has a good inhibition effect on human hepatocarcinoma cell lines HepG2 and Huh7; in seven tested 5-hydrogen-1,4-benzodiazepine compounds, when the concentration of the compound VII is 30 [mu]M, the rate of inhibiting the human hepatocarcinoma cell line HepG2 can be up to 70 percent, and the rate of inhibiting the human hepatocarcinoma cell line Huh7 can be up to 64 percent. The invention discloses the application of the type of compounds in preparation of a liver cancer treatment medicine; furthermore, the compounds are high in inhibition activity for hepatoma cells, so that the 5-hydrogen-1,4-benzodiazepine compound has a good development and application prospect in preparation of anti-liver cancer medicines.

The invention is directed to novel [1,4]benzodiazepine compounds useful as vasopressin receptor antagonists for treating conditions involving increased vascular resistance and cardiac insufficiency. Pharmaceutical compositions comprising [1,4]benzodiazepine compounds of the present invention and methods of treating conditions such as hypertension, congestive heart failure, cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, renal vasospasm, renal failure, cerebral edema and ischemia, stroke, thrombosis, or water retention are also disclosed.